17 Fischer, Thomas Dietlein, Felix Bongartz, Detlev Klehr, Martin Zimmermanns, Beate Schmidt, Matthias Mohr, Angela Mohr, Fabian Sudbrock, Ferdinand Krapf, Philipp Drzezga, Alexander Dietlein, Markus Schomäcker, Klaus AG Boecker International journal of molecular sciences International journal of molecular sciences Molecular Diversity Preservation International Basel 1422-0067 10.3390/ijms251910737 10737 19 25 Preliminary studies on a radioactive antibody against the neural cell adhesion molecule (NCAM) demonstrated a significant accumulation of [131I]I-ERIC1 in neuroblastoma tumor cells in mice. This study aims to validate the therapeutic efficacy and potential adverse effects of these radioactive immunoconjugates (RICs) in neuroblastoma-bearing mice. To determine the highest tolerated dose, healthy SCID mice received 1 to 22 MBq of [131I]I-ERIC1, with the survival time measured. Tumor response was evaluated by administering 0.8 to 22 MBq of [131I]I-ERIC1 to neuroblastoma-bearing mice and assessing tumor size and systemic toxicity through body weight, blood counts, and survival. It was observed that doses up to approximately 3 MBq per animal (150 MBq/kg) were well tolerated, whereas higher doses resulted in systemic toxicity and death. The neuroblastomas exhibited a dose-dependent response, with optimal therapeutic efficacy achieved at 1.8-2.5 MBq per animal (90-125 MBq/kg), significantly extending survival by a factor of five. The antibody ERIC1 is a promising vehicle for the transport of beta emitters into NCAM-positive tumor tissue. An optimal dosage of the [131I]I-ERIC1 antibody can be established with a balance of tumor-static effects and adverse effects, resulting in a marked extension of survival time. PUB:(DE-HGF)16, ; 0, ; Animals Neuroblastoma: pathology Neuroblastoma: metabolism Neuroblastoma: drug therapy Mice Iodine Radioisotopes: adverse effects Cell Line, Tumor Neural Cell Adhesion Molecules: metabolism Humans Mice, SCID Xenograft Model Antitumor Assays Immunoconjugates: pharmacology Female Antibodies, Monoclonal: therapeutic use Antibodies, Monoclonal: pharmacology Journal Article 2024 DZNE-2024-01213 2024 pmc:PMC11476365 pmid:39409066 https://pub.dzne.de/record/272592 https://doi.org/10.3390/ijms251910737